The extracellular matrix (ECM) is composed of a diverse set of macromolecules, including both proteins and polysaccharides, which form the three dimensional environment within which cells exist in the body and constitute the space filling material between cells. The ECM can also be organized into a sheet-like layer known as the basal lamina or basement membrane. The ECM consists primarily of molecules that are secreted locally and assemble into a scaffold that stabilizes and supports the physical structure of cell layers and tissues. However, rather than being merely an inert substrate for cell attachment, the ECM constitutes an environment that is rich in biological information. It is recognized that the ECM, and various biomolecules associated with it (e.g., secreted locally or transported to a particular site from elsewhere), exert a significant influence on many aspects of cell behavior and phenotype, regulating processes such as migration and proliferation, influencing cell development and differentiation, and affecting cell shape and function. The structure of the ECM is, in turn, influenced by the cells within it. Not only do these cells secrete many ECM constituents, but they also help to pattern the matrix. Thus it is evident that cell ECM interactions are of vital importance. There remains a need for synthetic compositions and materials for tissue engineering purposes that would allow the creation of a cellular environment that mimics important aspects of the native cellular environment without the disadvantages associated with products derived from natural sources. For applications involving implantation into the body, there remains a particular need for such compositions and materials that elicit no or minimal immune or inflammatory response and for compositions and materials that are degradable within the body. In addition, there remains a need in the art for compositions and materials that would influence cell properties and functions in desirable ways.
It has previously been reported that a class of designer self-assembling peptide scaffolds have wide application including for three-dimensional (3-D) cell culture, drug delivery, regenerative medicine and tissue engineering [1a]-[5a]. The class of self-assembling peptide materials can undergo spontaneous assembly into well-ordered nanofibers and scaffolds, ˜10 nm in fiber diameter with pores between 5-200 nm and over 90% water content [6a]. These peptide scaffolds have 3-D nanofiber structures similar to the natural extracellular matrix including collagen. Furthermore, the scaffolds are biodegradable by a variety of proteases in a body with superior biocompatibility with tissue [7a]. Moreover, these scaffolds can be modified and functionalized by direct extension of peptides with known biologically functional peptide motifs to promote specific cellular responses. One family of these peptide scaffolds, functionalized RADA16 has been studied for bone, cartilage, neural regeneration and angiogenesis promotion [8a]-[11a].
In the treatment of periodontal disease, a number of surgical techniques have been developed to regenerate periodontal tissue, including guided tissue regeneration [12a]-[14a], bone grafting [15a], [16a], enamel matrix derivative [17a]-[19a] and the use of growth factors [20a]-[25a]. However, there are concerns associated with use of these animal-derived biomaterials including, for example, the risk of transferring infection agents from animals to human and the difficulty of handling animal-derived biomaterials. Therefore, there remains a need in the art for improved methods for periodontal tissue regeneration.